Chapter 176: Sensorineural Hearing Loss in Children

Patrick E. Brookhouser
Early identification of educationally significant sensorineural hearing impairment in
young children, which varies in incidence from 1:1000 to 1:2000 depending on the population
studied, should be a major public health priority. Early (re)habilitative intervention, as
provided under Public Law 94-457, is a prerequisite for the development of age-appropriate
speech and language skills by school age, to provide a basis for attaining literacy skills.
Credible research supports the existence of a critical period in the first years of life for
optimal acquisition of speech and language. The absence of adequate auditory stimulation in
the young infant may also impair the full development and maturation of central auditory
pathways. Universal hearing screening for all newborns would be a laudable goal, but
behavioral measures (both automated and direct observation) have proven too labor intensive,
as well as unreliable, and auditory brain stem response testing is too technologically
sophisticated and costly for general acceptance by clinicians. Evoked otoacoustic emission
testing may prove to be the long-awaited, cost-effective objective evaluation tool, but present
clinical practice focuses on evaluation of neonates and infants who are identified as being at
risk for hearing impairment. The major argument against limiting early identification efforts
to such targeted testing of high-risk populations is data indicating that as many as 50% of
infants with significant hearing loss may be missed.
In 1982 the Joint Committee on Infant Hearing recommended seven criteria for
identifying infants at risk for hearing impairment. Revised recommendations were published
in 1991 (Bess, 1991) that expand the risk criteria to include not only neonates (birth to 28
days) but also infants (29 days to 2 years). As many as 2% to 5% of neonates manifesting
high risk factors can be confirmed as having moderate to severe sensorineural hearing loss.
Additionally, recommendations were made regarding optimal audiologic screening protocols
and early intervention strategies for hearing-impaired infants and their families.
The high risk factors identified for neonates can be broadly classified in four
categories: family history, physical findings, events during birth and postnatal hospital stay,
and infections. A family history of congenital or delayed-onset childhood sensorineural
hearing loss (SNHL) should serve as a red flag for referral of the infant for early audiologic
evaluation. High-risk physical findings include birth weight less than 1500 g (3.3 lb);
craniofacial anomalies involving the ear, skull, and mouth region; and stigmata associated
with a hearing loss syndrome, such as white forelock Waardenburg's syndrome). Severe
depression of vital body systems at birth is reflected by a low Apgar score (0 to 3 at 5
minutes), delayed spontaneous respirations (beyond 10 minutes), and persistent hypotonia
during the first 2 hours of life. In addition to these indicators, significant occurrences during
the neonatal period include hyperbilirubinemia requiring exchange transfusion, prolonged
mechanical ventilation, and treatment with ototoxic medications (for example, gentamicin,
tobramycin, kanamycin, streptomycin). Infections with the potential to damage hearing may
be acquired prenatally (for example, toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes)
or postnatally (for example, bacterial meningitis).


In addition to risk factors for neonates, infants (29 days to 2 years) may sustain
skull/temporal bone trauma or contract other infectious diseases with potential for causing
SNHL (for example, measles or mumps). Neurodegenetative disorders in infancy (for
example, Tay-Sachs disease, myoclonic epilepsy) should also prompt a referral for hearing
evaluation. Finally, concern expressed by a parent or surrogate care giver about an infant's
hearing, speech and language acquisition, or general development should alert the clinician
to the need for audiologic evaluation. The axiom "moter is always right" is worth
remembering when deciding whether to refer an infant for testing. Because behavioral
audiologic testing of hearing in neonates and some infants is fraught with methodologic
problems, it is essential to refer the high-risk neonate for auditory brain stem response (ABR)
evaluation, optimally before hospital discharge. If this is not feasible, evaluation by 3 months
of age is acceptable, but a delay beyond 6 months is unwaranted. It is important to continue
follow-up of those infants with absent or abnormal ABRs or a family history of progressive
hearing loss. The conventional "click" stimulus used to elicit an ABR in most centers is
accurate in assessing auditory acuity for higher frequencies (that is, above 2000 Hz), so that
a valid and repeatable behavioral audiogram should be obtained as soon as practicable.
Appropriate (re)habilitative intervention should be initiated immediately after a sensorineural
hearing loss has been confirmed. Local school districts are obligated to provide and coordinate
such intervention programs for hearing impaired children living within their boundaries.
The risk factors that identify those neonates, birth to 28 days, who are at risk for
sensorineural hearing impairment include the following (ASHA, 1991):
1. Family history of congenital or delayed-onset childhood sensorineural impairment.
2. Congenital infection known or suspected to be associated with sensorineural hearing
impairment such as toxoplasmosis, syphilis, rubella, cytomegalovirus, or herpes.
3. Craniofacial anomalies, including morphologic abnormalities of the pinna and ear
canal, absent philtrum, and low hairline.
4. Birth weight less than 1500 g (3.3 lb).
5. Hyperbilirubinemia at a level exceeding indication for exchange transfusion.
6. Ototoxic medications including but not limited to the aminoglycosides used for
more than 5 days (for example, gentamicin, tobramycin, kanamycin, streptomycin) and loop
diuretics used in combination with aminoglycosides.
7. Bacterial meningitis.
8. Severe depression at birth, which may include infants with Apgar scores of 0 to 3
at 5 minutes or those who fail to initiate spontaneous respiration by 10 minutes or those with
hypotonia persisting to 2 hours of age.
9. Prolonged mechanical ventilation for a duration equal to or greater than 10 days (for
example, persistent pulmonary hypertension).


10. Stigmata or other findings associated with a syndrome known to include
sensorineural hearing loss (for example, Waardenburg or Usher syndrome).
The factors that identify those infants, 29 days to 2 years, who are at risk for
sensorineural hearing impairment include the following:
1. Parent or care giver's concern regarding hearing, speech, language, or developmental
2. Bacterial meningitis.
3. Neonatal risk factors that may be associated with progressive sensorineural hearing
loss (for example, cytomegalovirus, prolonged mechanical ventilation, and inherited
4. Head trauma, especially with either longitudinal or transverse fracture of the
temporal bone.
5. Stigmata or other findings associated with syndromes known to include
sensorineural hearing loss (for example, Waardenburg or Usher syndrome).
6. Ototoxic medications including but not limited to the aminoglycosides used for
more than 5 days (for example, gentamicin, tobramycin, kanamycin, streptomycin) and loop
diuretics used in combination with aminoglycosides.
7. Children with neurodegenerative disorders such as neurofibromatosis, myoclonic
epilepsy, Werdnig-Hoffmann disease, Tay-Sachs disease, infantile Gaucher's disease,
Niemann-Pick disease, any metachromatic leukodystrophy, or any infantile demyelinating
8. Childhood infectious diseases known to be associated with sensorineural hearing
loss (for example, mumps, measles).
Neonates, birth to 28 days, who manifest one or more items on the risk criteria should
be screened, preferably under the supervision of an audiologist. Optimally, screening should
be completed before discharge from the newborn nursery but no later than 3 months of age.
The initial screening should include measurement of the auditory brain stem response (ABR)
(ASHA 1989). Behavioral testing of newborn infants' hearing has high false-positive and
false-negative rates and is not universally recommended. Because some false-positive results
can occur with ABR screening, ongoing assessment and observation of the infant's auditory
behavior are recommended during the early stages of intervention. If the infant is discharged
before screening or if ABR screening under audiologic supervision is not available, the child
should be referred for ABR testing by 3 months of age but never later than 6 months of age.
The acoustic stimulus for ABR screening should contain energy in the frequency
region important for speech recognition. Clicks are the most commonly used signal for
eliciting the ABR and contain energy in the speech frequency region (ASHA, 1989). Pass
criterion for ABR screening is a response from each ear at intensity levels 40 dB nHL or less.

Because the majority of genetic hearing loss is inherited in a recessive manner. intrauterine infections. birth. and craniofacial deformities. In addition to a detailed prenatal. head trauma. Infants who fail the screen should be referred for a comprehensive audiologic evaluation.Transducers designed to reduce the probability of ear-canal collapse are recommended. If a family history of hearing loss is identified. nose. or noise damage. For infants less than 6 months of age. ear. who exhibit one or more items on the risk criteria should be screened as soon as possible but no later than 3 months after the child has been identified as at risk. speech/language disorders. dystopia canthorum. and café-au-lait spots. meningitis. 28 days to 2 years. such as kidney disorders. behavioral testing using a conditioned response or ABR testing is appropriate. behavioral testing (6 months). A careful physical examination must involve not only an assessment of the ears but also a search for subtle findings such as preauricular or branchial pits. and postnatal history for the child. intracranial tumors. it is very important to rule out marital consanguinity in the family history. and a speech/language pathologist to assess oral motor function and linguistic development. thyroid disease. sudden death at a young age. Consultation in pediatric neurology and neuroradiology should also be easily available. a psychologist to assess the child's cognitive abilities. blue sclerae. a pediatrician skilled in detecting subtle findings associated with deafness syndromes. progressive blindness. then the screening process will be considered complete except in those cases where there is a probability of progressive hearing loss (for example. If consistent electrophysiologic responses are detected at appropriate sound levels. pulmonary hypertension. but no 4 . because family oral tradition ascribes each case to an extrinsic cause such as mastoid disease. ABR screening is recommended. as well as features that accompany syndromes. It is important to realize that many families with genetic deafness fail to recognize the heritable nature of the disorder. and acoustic immitance measures (see ASHA 1989 Guidelines for recommended protocols by developmental age). Infants. and audiologic follow-up. If the results of an initial screening of an infant manifesting any risk criteria are equivocal. a genetic counselor. or received medications in doses likely to be ototoxic). Specific physical findings associated with deafness syndromes are detailed in the subsequent text. For infants older than 6 months. an educator of the deaf with expertise in early intervention. family history of delayed onset. an exhaustive pedigree should be constructed. otologic. then the infant should be referred for general medical. This evaluation may include ABR. or infants who had chronic lung disease. and café-au-lait spots. including at least three generations. Evaluation of Young Hearing Impaired Child The comprehensive evaluation of a child with educationally significant hearing impairment requires the coordinated efforts of a specialty team that should include an otolaryngologist experienced with children. a complete family history should be obtained that includes hearing loss. heterochromia iridis. degenerative disease. and throat disorders. a pediatric ophthalmologist with competence in electroretinography. facial asymmetry. a pediatric audiologic team competent with both behavioral and electrophysiologic testing. A thorough case history provides the foundation for the remainder of the evaluation.

or anacusic). With the declining incidence of non-genetic etiologies such as prenatal rubella. Additionally. The utility of CT scans for assessing profoundly deaf children for cochlear implant candidacy has resulted in increased use of this diagnostic modality in recent years. standing on one foot). which may also be important in determining the cause of delayed gross motor skill development (such as sitting unsupported. in children raises the specter of possible perilymphatic fistula (PLF). will prove inconclusive in 30% to 40% of cases. measles. Serologic tests aimed at detecting congenital syphilis and toxoplasmosis. After that. are advisable. the degree of loss (that is. The role that autoimmune disorders play in the etiology of SNHL in children is presently unclear. the audiometric configuration and symmetry of the impairment. Although preoperative confirmation of PLF remains elusive. type 1) and with hearing loss attributable to such nongenetic etiologcies as bacterial meningitis. If hematuria is present. Cytomegalovirus infection presents a diagnostic quandary. Ophthalmologic evaluation is critical because the visual system assumes an even more important neurosensory role in a child with impaired auditory acuity. and thyroid studies. early detection of coexisting retinitis pigmentosa. sensorineural. or mixed). mild. additional renal studies (such as ultrasound) should be undertaken. but a negative result must be considered inconclusive on the basis of reported series. blood sugar. conductive. antibodies to perinatally or postnatally acquired CMV can obscure the diagnosis. and judgments regarding the cost effectiveness of studies aimed at detecting such disease processes must await evidence regarding their prevalence. Basic laboratory studies should include complete blood count with differential and sickle cell preparations. basic blood studies: chemistries. The pediatric audiologic evaluation must determine the type of hearing loss (that is. a monitored fistula test seems a reasonable course in these cases. with serial assessment. both of which are potentially treatable. mumps and Haemophilus influenzae meningitis. Many parents are anxious to determine the etiology of their child's loss for prognostic and family planning considerations. if indicated. A positive fistula test may be helpful. probably within the first month or two. The relatively low yield and high cost of such studies make their uniform application problematic. Vestibular dysfunction may coexist with hearing loss in some children with genetic deafness (for example. Clinicians serving the needs of these families must be prepared to 5 . can influence (re)habilitative decisions. lipids. but confirmation of true congenital infection must be based on positive serology obtained very early in life. as well as inner ear or internal auditory canal anomalies or lesions in cases of SNHL. Usher's syndrome. with electroretinography.finding should be disregarded until genetic consultation has been obtained. A diligent search for etiology of SNHL in a child. Temporal bone imaging studies are helpful in identifying middle ear anomalies in children with conductive or mixed losses. Knowledge of the rubella vaccination status of the mother should determine the necessity for pursuing that diagnosis. and urinalysis. with or without vertigo. It is likely that CMV accounts for a significant percentage of childhood deafness. The availability of computerized rotational testing has facilitated vestibular system evaluation in young children. severe. moderate. creatinine. Progressive and fluctuating SNHL. BUN. the stability or progression of the loss. genetic hearing loss will affect an increasing percentage of newly identified cases. and finally. walking. utilizing state of the art techniques. profound.

postnatal) onset. age of onset. infections. It would seem most helpful to classify SNHL cases broadly in a matrix as genetic versus nongenetic and congenital versus delayed (that is. and they may be classified on the basis of other organ systems involved. ocular. Clearly. such as trauma. Individual alterations of forms or structure A malformation is a defect in the morphology of an organ or body region occurring because the underlying developmental potential of the involved organ was intrinsically abnormal. perinatally. disorders. and unilateral or bilateral. whereas certain nongenetic hearing impairments (for example. 6 . Patterns of Dysmorphology Based on the classification by Spranger et al (1982). presence or absence of progression. craniofacial/cervical. By definition. radiation. and 25% to 30% are sporadic cases of uncertain etiology. the resulting morphologic anomaly is called a disruption. 20% to 25% of cases are attributable to identifiable environmental causes. and "other". hearing loss only) are generally based on audiologic characteristics. or chromosomal. rubella deafness) are present at birth. If an organ's developmental potential was normal and extrinsic factors. Genetic forms of hearing loss may be congenital or delayed in onset. neurologic.address their concerns regarding the lack of a definitive diagnosis. with the remainder classified as X-linked. or later in life. cause the defect. or there may beno associated syndrome. Rapidly expanding knowledge regarding genetic hearing loss should lead to techniques for the prenatal or early postnatal diagnosis of these disorders even if clinical manifestations are delayed for months or years. a number of terms can be used to describe patterns of dysmorphology. and mode of inheritance. Classifications of hearing impairments not associated with syndromes (that is. disruptions cannot be inherited because they are sporadic occurrences. or pharmaceuticals. integumentary. skeletal. many genetic hearing losses are not congenital. Genetic Hearing Loss It has been estimated that 50% of childhood sensorineural hearing impairment is due to genetic factors. Several detailed etiologic classifications of SNHL in children have been suggested. progressive or nonprogressive. occurring prenatally. metabolic. they may be part of a syndrome (that is. At least 100 genetic syndromes that involve hearing loss have been identified. Approximately 75% to 80% of genetic hearing loss is generally attributed to autosomal recessive genes and 18% to 20% to autosomal dominant genes. renal. The use of terminology such as genetic versus acquired and congenital versus acquired can be confusing. there is only hearing loss). involving other identifiable physical characteristics in other systems). (that is.

can result from various intrinsic and extrinsic forces operative in several different developmental environments. For any particular trait. and E . association is a statistical instead of an etiopathogenetic construct that serves to alert clinicians to possible occult associated anomalies after one defect has been identified.genital hypoplasia. Each pair of chromosomes carries a distinctive set of gene loci for which there may be several alternative codes or alleles. not meeting strict criteria for classification as a polytopic field defect.heart defects. A . Solitary acoustic neuromas and multiple neurofibromatoses are examples of dysplasias. as exemplified by osteogenesis imperfecta resulting from a defect in connective tissue. A dysplasia may involve multiple organs. The Robin sequence (also known as Pierre Robin syndrome). Patterns of morphologic defects A polytopic field defect results from perturbation of a single developmental field. may be sporadic or multifactorial in etiology. R . shape. or syndrome. A parent who is heterozygous for an autosomal dominant gene has a 50% chance of transmitting it to each 7 . Basic Genetic Principles Human genes are arranged linearly on 22 pairs of autosomes and 1 pair of sex chromosomes. and glossoptosis.choanal atresia. consisting of micrognathia. An autosomal dominant allele is phenotypically expressed in either the homozygous or heterozygous state. whereas the term sequence describes a pattern of several anomalies resulting from a single cause such as a preexisting anomaly or a mechanical force.retarded growth and development and/or CNS anomalies. In reality. cleft palate. H .Intrinsic or extrinsic mechanical forces can produce a deformation in which a part of the body assumes an abnormal position. which is determined by the nature and interaction of the two alleles. CHARGE association consists of the following: C . G . in two or more individuals. which could include disorders resulting from chromosomal abnormalities or genetically determined morphogenetic deviances. An X-linked (that is. the genotype may be comprised of two identical alleles (homozygous) or two different alleles (heterozygous). Intrauterine contrainst is an example of such a deforming force. The physical expression of the trait in an individual is called the phenotype. and may result from a genetic mutation. Malformation syndromes usually have an identifiable cause. A syndrome is a pattern of multiple anomalies presumed to be pathogenetically related but not meeting the qualifications for classification as a single sequence or a polytopic field defect. Abnormal cellular organization within tissues is classified as a dysplasia. which taken together constitute what might be called a design manual for the human body. whereas an autosomal recessive allele is expressed only in the homozygous state. sequence.ear anomalies and/or deafness. or form. sex chromosome-linked) recessive gene will also be expressed in the hemizygous condition in the male because the Y chromosome does not carry a complementary allele.coloboma. Association describes a nonrandom occurrence of multiple anomalies. A malformation or disruption may be the underlying cause of a sequence.

Waardenburg syndrome (WS 1). Inner Ear Structural Malformations By the beginning of the ninth week of gestation. Studies utilizing modern temporal bone imaging reveal subtle or severe anomalies of the inner ear in about 20% of children with congenital sensorineural hearing loss. but each male child has a 50% chance of inheriting the gene. with the nature and severity of each phenotype depending on the amount and origin of the material involved. and two genetic loci are said to be linked when their alleles are transmitted together more frequency than expected by chance. with about 65% being bilateral and the remainder unilateral.75 turns). 176-1). but 100% of the daughters of an affected male will inherit his only X chromosome and thus carry the abnormal gene. Chromosomal abnormalities involving autosomes result from extra or deficient chromosomal material being present in each cell. and branchio-oto-renal syndrome (BOR). monosomy. Other autosomal trisomies are almost always lethal. Phenotypic expression may be modified by environmental influences or interaction with other genes. An X-linked recessive trait is not usually expressed in a heterozygous female. Variable expressivity is also characteristic of dominant genes in that different family members may show diverse manifestations of the gene. Genetic material may be randomly exchanged (that is. the linked focus can be determined. 176-2). which would be phenotypically expressed. a phenomenon called decreased penetrance. Genetic Linkage Analysis Genetic linkage analysis is the process of determining the precise chromosomal location of a specific gene. whereas trisomy 13 (Patau's syndrome) and trisomy 18 (Edward's syndrome) are less common and more severe. the cochlea reaches full growth (2. and the phenotypic expression may be quite severe or even fatal. None of an affected male's sons inherit his X chromosome with the abnormal gene. There is a 50% chance that each of a female carrier's daughters would also inherit the gene. Offspring of heterozygotic carriers of an autosomal recessive gene have a 25% recurrence risk (Fig. In patients with trisomy. as is the presence of a single chromosome of a pair. crossover) between two members of a chromosome pair during cell mitoses.child (Fig. These DNA probes have already played an important role in linkage studies successfully identifying specific chromosomal loci of multiple genes responsible for Usher syndrome (USH 1 and USH 2). Dominant genes may not be phenotypically expressed in all individuals who are heterozygous for the gene. Arrest in normal development (agenesis) or aberrant development (dysgenesis) of inner ear structures may result in hearing impairment. If the chromosomal location of one gene is known (a marker gene). three copies of a given chromosome are present. Phenotypes associated with abnormalities of sex chromosomes are generally less severe. Chromosomal deletions (absent segments) or duplications (extra material) may be present. 8 . Restriction fragment length polymorphisms are markers based on variations in DNA sequence rather than on gene product. Trisomy 21 or Down's syndrome is the least severe autosomal trisomy.

Refsum's. Treacher Collins. but the interscalar septum is absent in the upper coils. and such intervention is contraindicated. The organ of Corti is generally poorly differentiated with a deformed tectorial membrane and collapsed Reissner's membrane. with enough residual low-frequency hearing to benefit from amplification. are normally differentiated in patients with Scheibe's aplasia. including the utricle and semicircular canals. has been associated with early-onset SNHL. An enlarged vestibular aqueduct. although labyrinthitis ossificans. High-frequency hearing loss is the rule in these patients. Usher's. which includes unilateral or bilateral sensorineural hearing loss in 20% of cases. An obligate carrier may not have any detectable phenotypic expression because of decreased penetrance. but conventional amplification and cochlear implantation are not efficacious for obvious reasons. Autosomal Dominant Disorders An autosomal dominant syndrome might be expected to be easily identified by a positive family history of classical dominant inheritance and a recognizable phenotype. Initial hopes that endolymphatic sac surgery in these patients might be beneficial proved incorrect. The anomaly is inherited in an autosomal dominant fashion. In Alexander's aplasia. and Wildervaank's syndromes. Scheibe's is the most common aplasia and has been observed in temporal bones from patients with Jervell and Lange-Nielsen. observed radiographically. may be unilateral or bilateral. In fact. Vibrotactile devices have been of some benefit with these patients. two distinct types of Waardenburg's syndrome are distinguishable.Complete agenesis of the petrous portion of the temporal bone occurs in Michel's aplasia. It is postulated that the deformity results from a development arrest at approximately the sixth week of gestation. Variable expressivity is observed with Waardenburg's syndrome. Waardenburg. but the disorder is still transmitted in a dominant fashion. and Waardenburg's syndromes. Temporal bone imaging plays an essential role in confirming the diagnosis. cochlear duct differentiation at the level of the basal coil is limited. The bony labyrinth and superior portion of the membranous labyrinth. In Mondini's aplasia the basal coil of the cochlea can be clearly identified. which assume a cloacal form. with hearing loss 9 . which is usually bilateral and may be accompanied by vertigo. as well as pigmentary anomalies: white forelock in 20% to 30% of cases. and synophyrs. based on the presence (WS-1) or absence (WS-2) of dystopia canthorum. with resultant effects on the organ of Corti and ganglion cells. as occurs following meningitis. the family history might be negative. broad nasal root. An aggressive program of early intervention with conventional amplification is advisable in cases with residual neurosensory structures. Inherited as an autosomal recessive trait. variation in expressivity may be reflected in different phenotypic characteristics in affected family members. and craniofacial features such as dystopia canthorum. Affected ears are anacusic because of the absence of sensory and neural inner ear structures. premature graying. and has been described in a number of disorders. including Pendred's. and vitiligo. Clinically. can present a similar appearance. If a new mutation has occurred. heterochromia iridis. which is inherited as an autosomal dominant trait.

with an incidence of about 1:3000 persons. conductive. downward slanting palpebral fissures. The craniofacial features of Treacher Collins syndrome (mandibulofacial dysostosis) may include microtia. Sensorineural or mixed hearing loss is present in about 15% of cases. aural meatal atresia. Malar hypoplasia. microtia and craniofacial abnormalities. Bilateral acoustic neuromas are present in 95% of cases with central neurofibromatosis (NF-2). which generally includes many café-au-lait spots and cutaneous neurofibromas but acoustic neruomas (typically unilateral) in only 5% of cases. characterizes the face of affected individuals. coloboma of the lower eyelids. which is genetically distinct from the classical form. blindness. myopia that may be accompanied by retinal detachment or cataracts. Sensorineural loss and vestibular dysfunction may also be present. In branchiootorenal (BOR) or Melnick-Fraser syndrome. Cutaneous tumors are most common. Both types of neurofibromatosis are inherited as autosomal dominant traits with high penetrance but variable expressivity. High mutation rates characterize both disorders. Persons affected by neurofibromatosis may present with café-au-lait spots (light brown. 1992). Features in individuals with Stickler's syndrome may include a small jaw. Café-au-lait spots and cutaneous neurofibromatosis in NF-2 patients are fewer than observed in von Recklinghausen's disease. Symmetric facies and bilateral eyelid coloboma distinguish Treacher Collins from Goldenhar's syndrome and other oculoauricular vertebral syndromes that involve similar. hypermobility and enlargement of joints with early adult-onset arthritis. Two distinct forms have been identified clinically. Presenting signs and symptoms of the bilateral lesions may not be noted until early adulthood. 10 . variable-sized pigmented spots) and multiple fibromatous tumors. and a hypoplastic mandible. peripheral nerves. and conductive hearing impairment about 30% of the time. 1990). so that only 40% of gene carriers will actually demonstrate the phenotype. and occasional spondyloepiphyseal dysplasia. often with a cleft palate (Robin sequence).being more frequent in WS-2. Initial linkage analysis results assign a locus for WS-1 to the 2q37 region of the number 2 chromosome (Foy et al. Linkage analysis studies have recently identified the responsible gene to be on chromosome 8q (Kimberling. The oculoauriculovertebral (OAV) spectrum is sporadic and thought to be multifactorial. The gene for at least one form of NF-2 has been assigned to chromosome 22 by linkage analysis. The hearing loss may be sensorineural. Delayed-onset conductive or mixed hearing impairment may begin in childhood but usually presents in adulthood. with underdeveloped zygomatic arches. whereas Treacher Collins syndrome is transmitted as an autosomal dominant trait. Otosclerosis appears to be transmitted by an autosomal dominant pattern with decreased penetrance. and viscera may also be involved. but the central nervous system. detectable by ultrasound or intravenous pyelography. and SNHL may result from CNS lesions. but unilateral. or mixed. the more common beign classic neurofibromatosis (von Recklinghausen's disease). ear pits (possibly tags) or cervical fistulas are present as are renal findings ranging from agenesis with renal failure to minor asymptomatic renal dysplasia. Mental retardation.

0/100. high frequency. variable in age of onset and rate of progression. based on severity of the hearing loss and the extent of vestibular system involvement. A severe congenital type may present with intrauterine fractures severe enough to threaten fetal viability. Kimberling and coworkers have identified chromosome 11q as the probable site of the gene for USH 1 that occurs in patients who are not of Acadian background and do not reside in Louisiana (Kimberling. Nonsyndromic Autosomal Dominant Hearing Loss Dominant progressive hearing loss (DPHL) is a type of nonsyndromic. and subnormal electroreginographic (ERG) patterns have been observed in affected children as young as 2 to 3 years of age. The perchlorate discharge test demonstrates abnormal organification of nonorganic iodine in these patients. SNHL is associated with abnormal iodine metabolism resulting in a euthyroid goiter. before retinal changes are evident fundoscopically. noncongenital sensorineural hearing loss. mixed.000 in the USA. More recently. 176-3). This disorder is transmitted as an autosomal dominant trait with variable expressivity and incomplete penetrance. transmitted as an autosomal dominant trait. Van der Hoeve's syndrome is a subtype of osteogenesis imperfecta in which progressive hearing loss begins in early childhood. This disorder affects about one half of the 16. but carriers are asymptomatic. but initial frequency involvement and the rate of progression vary among families. It is idiopathic and differs from otosclerosis by the absence of ossicular and otic capsule involvement and from presbyacusis by the earlier age of onset. Linkage analysis studies have localized the gene for USH 2 to the 1q32 region of chromosome 1 (Kimberling. 11 . 1990). with approximately one half of cases involving recognizable syndromes. Sensorineural hearing loss and retinitis pigmentosa characterize Usher syndrome.000 in Scandinavia and 4. USH 1 and USH2. are distinguishable. 1992). or sensorineural). and low frequency. which has an estimated frequency of 3. bilateral profound hearing loss and absent vestibular function. In the autosomal recessive disorder Pendred's syndrome. making definitive diagnosis in small kindreds difficult unless other syndromic components are identified. Clinically.4/100. hearing loss (conductive. About 80% of genetic deafness in childhood is inherited in an autosomal recessive fashion. mid frequency. and hyperelasticity of joints and ligaments. at least two subtypes. Minimal peripheral fixation of a markedly thickened stapedial foot plate is present in a typical case of osteogenesis imperfecta hearing loss.Osteogenesis imperfecta is characterized by bone fragility. All types of DPHL eventually progress to severe or profound hearing loss. histopathologic studies of stapedial foot plates in each disorder demonstrate significant differences. The age at which the more common "tarda" variety becomes clinically apparent is variable. Ophthalmologic evaluation is an essential part of the diagnostic workup. Although some investigators have postulated a relationship between osteogenesis imperfecta and otosclerosis. Konigsmark and Gorlin (1976) defined four types of DPHL: early onset. whereas USH 2 patients have moderate hearing losses and normal vestibular function (Fig. blue (clear) sclerae.000 deaf/blind persons in the USA. Patients with USH 1 present with congenital. and exogenous thyroid hormone is the therapy of choice. Variation in penetrance and expressivity is less pervasive than with dominant disorders.

The progressive hearing impairment may not become clinically evident until the second decade of life. and early-onset. with an excessively wide space between the first and second toe. and death from uremia before 30 years of age was the rule before the availability of renal dialysis and kidney transplantation. development of pseudoglioma. with onset in the second or third decade. Progressive sensorineural hearing loss. Although genetic heterogeneity may be involved in some cases. Electrocardiographically. Beta-adrenergic blockers have proven effective in treating the disorder. Characteristics associated with otopalatodigital syndrome may include hypertelorism. a severe. The renal disease may cause hematuria in infancy but generally remains asymptomatic for several years before onset of renal insufficiency. opacification.In patients with Jervell and Lange-Nielsen syndrome. rapidly progressive and moderately slowly progressive. and cleft palate. Renal involvement is especially severe in males. craniofacial deformity involving the supraorbital area. congenital moderate.5 years to profound loss by 6 years of age. small nose. the gene for the X-linked form of Alport's codes for a collagen gene (COL4A5) on the X chromosome. 12 . congenital sensorineural hearing impairment is inherited in a recessive pattern together with a cardiac conduction defect that can produce syncopal episodes early in life and even sudden death. flat midface. Affected individuals are also short in stature with broad fingers and toes that vary in length. large T waves and prolongation of the QT interval are observed. In Alport's syndrome SNHL is associated with renal impairment of varying severity. affects approximately one third of individuals with this sex-linked disorder. Konigsmark and Gorlin (1976) described three subtypes of nonsyndromic recessive SNHL: congenital severe. An associated conductive hearing loss usually results from an ossicular malformation. Wildervaank's syndrome is comprised of the Klippel-Feil malformation involving fused cervical vertebrae. and cranial nerve VI paralysis causing retraction of the eye on lateral gaze. In Norrie's syndrome congenital or rapidly progressive blindness. sensorineural or mixed hearing impairment. Wildervaank's syndrome is almost always observed in females because of the high degree of lethality associated with the X-linked dominant form in males. which usually progresses rapidly from onset at age 1. Two types of nonsyndromic congenital severe sensorineural hearing loss have been described: early-onset. and ocular degeneration resulting in microphthalmia are observed. so that an electrocardiogram should be performed on all children with early-onset hearing loss of uncertain etiology. Sex-Linked Disorders Approximately 6% of nonsyndromic profound losses in males may be attributable to sex-linked disorders.

cleft lip/palate) syndromes. Consideration of the usual pattern of penetrance of a gene must be considered in counseling regarding recurrence risks for autosomal dominant disorders. epibulbar dermoids. and the microtia/hemifacial microsomia/Goldenhar's spectrum. conductive. The specific etiology of a hearing loss may still remain uncertain after an intensive. but if parents have disparate etiologies. generally present as females with gonadal dysgenesis. Turner's syndrome patients. with hearing losses of uncertain etiology. and coloboma of the upper lip. Goldenhar's syndrome (oculoauriculovertebral dysplasia) has also been described as being inherited in an autosomal dominant pattern in some families. If both parents have identical recessively inherited deafness.Multifactorial Genetic Disorders Some genetic disorders appear to result from a combination of genetic factors interacting with environmental influences. Autosomal Chromosomal Syndromes Middle ear and mastoid disease is often observed in Down's syndrome children. the recurrence rate would be 100%. or mixed hearing loss may be seen with Turner's syndrome. for example. evaluation. 13 . Each additional normal hearing child born to such a family reduces the probability of a genetic etiology with a consequet decrease in estimated recurrence risk. and often expensive. Genetic Evaluation and Counseling Family histories of persons with genetic hearing impairment often involve a number of marriages between deaf individuals. prognosis. A complete genetic evaluation involves diagnosis. Sensorineural. taking into account various possibilities. vertebral anomalies such as hypoplastic vertebrae or hemivertebrae in the cervical region. Bieber and Nance (1978) developed empiric risk tables based on an "averaged" risk. The averaged empiric risk cited for such a couple is 6%. the risk may be quite small. Recurrence risk for children of an individual with recessively inherited deafness depends on the genetic status of his or her mate. including the number of affected an unaffected children in the family. including careful delineation of the phenotype. which would decrease with each unaffected child born to them. Such multifactorial disorders associated with hearing loss include clefting (that is. If a normal hearing individual marries a person with sensorineural hearing loss of uncertain etiology. the range of recurrence risk for future offspring in a family whose only child has an unexplained hearing impairment is 10% to 16%. Reasonable criteria for obtaining cytogenetic studies would be the presence of two major malformations or a single major malformation with two or more minor malformations. short stature. their risk of having a hearing-impaired child could range from negligible (nongenetic or uncommon recessive) to 50% if the gene is a fully penetrant dominant one. and estimation of recurrence risk. Findings may include preauricular tags/pits. The recurrence risk in deaf x deaf marriages entirely depends on the etiology of the deafness. For instance. involving conductive hearing loss. and often a webbed neck or shield chest. monosomic for all or part of one X chromosome (X0).

permitting direct spread along meningeal and neural structures into the perilymphatic spaces. New diagnostic techniques. Rubeola and vaccinia viruses infected both perilymphatic and endolymphatic cells. 14 . These findings are consistent with a blood-borne spread of infection most likely via vessels of the stria vascularis. Epstein-Barr. Measles. Histopathologic studies of temporal bones from patients who were affected by prenatal rubella. adenoviruses.When both husband and wife have hearing losses of uncertain etiology. and CMV may also present with a meningoencephalitis. rubeola. varicellazoster. although two measles patients also revealed histopathologic evidence of endolabyrinthitis. Seroconversion studies and virus isolation from urine and nasopharyngeal secretions have confirmed an association of labyrinthitis with rubella. rubeola. mumps. hold promise for more specific diagnostic capability in the future. whereas mumps virus infected principally endolymphatic structures. Cytomegalovirus has been isolated from human labyrinthine fluids. Before the advent of an effective vaccine. mumps was a common etiology of acquired profound unilateral sensorineural hearing loss in childhood. mumps. The risk declines with the birth of each hearing child but increases to 62% if their firstborn is hearing impaired. sampling of peripheral umbilical blood. or cytomegalovirus (CMV) reveal evidence of an endolymphatic labyrinthitis with pathologic changes limited to the cochlear duct. where inflammatory changes may later progress to fibrosis. but these infections continue to play a significant role in the Third World. including fetal ultrasound. poliomyelitis. influenza virus infected mesenchymal cells in the perilymphatic system. Bordley and Kapur (1972) studied temporal bones of patients who suffered acute smallpox. and utricle. Effective immunization programs for rubella. most counselors assign an empiric risk for a deaf child of about 10%. rubeola. and mumps in developed countries have decreased their importance in the etiology of childhood hearing loss. mumps. influenza. Viral infections A number of viruses have been implicated as etiopathogenic agents for congenital and acquired hearing loss. Davis and Johnson (1976) demonstrated selective vulnerability of inner ear structures of experimental animals to specific viruses. and polymerase chain reaction technology. variola. whereas herpes simplex involvement was essentially limited to the sensory cells of the labyrinth. saccule. and parainfluenza viruses. or measles and found the most severe pathologic changes in the middle ears. Infectious Diseases Congenital and early-onset infectious disease Congenital and neonatal infections Infections acquired during the prenatal or perinatal/neonatal period occur in about 10% of all live births. In most instances these infections are asymptomatic or present non-specific findings. varicella (chickenpox). In newborn hamsters.

15% of cases. 15 . Microcephaly. and primary infection is accompanied by viral shedding that may persist for months to years. petechiae. About 1% to 4% of susceptible women will experience primary CMV infection during pregnancy. 10% to 15% are symptomatic. and blood transfusions. Higher SES women with evidence of CMV immunity at conception will deliver infants with congenital infection in 0. and prematurity also characterize the CID population.Cytomegalovirus infection Cytomegaloviruses (CMVs) are members of the herpes family that are widely prevalent in human populations in both developed and developing countries. virus in breast milk. CMV infection is endemic in child day-care centers. from mother to child) or horizontally from person to person. occurring in approximately 1% of all live births. The probability that her baby will have a harmful congenital CMV infection is decreased in the mother with recurrent infection. intrauterine growth retardation. Human CMV appears to be species specific with no known external reservoirs or animal vectors involved in transmission. and jaundice as common presenting findings. with hepatosplenomegaly. is currently the most common cause of intrauterine infection in humans. Of congenitally infected infants.0% (Fig. Although Hardy (1973) found that the gestational age of the fetus is the most important factor determining the extent and long-range consequences of congenital viral infections. whereas the congenital infection rate among offspring of immune lower SES mothers varies from 0.5% to 1. which is definitely diagnosed by isolation of the virus from neonates in the first few weeks of life. the time of greatest susceptibility for CMV is not known. fully 85% of fertile women demonstrate immunity. with a resultant fetal infection rate of 40%. In populations of higher socioeconomic status (SES) approximately 55% of women of childbearing age are CMV immune. and transmission of the virus from young children who acquire CMV at such centers to their pregnant mothers is important epidemiologically. including severe to profound sensorineural hearing impairment and such ocular abnormalities as chorioretinitis and optic atrophy in 25% to 30% of cases. with the remaining 45% susceptible to primary CMV infection. An additional 4% to 10% of infants acquire the infection during and after birth through such sources as cervical virus shedding. As many as 90% of children with true CID will develop severe mental and perceptual deficits by 2 years of age. Congenital CMV infection differs from rubella and toxoplasmosis in that the virus can be transmitted in utero in the course of both primary maternal infection and infection resulting from reactivation of latent virus in immune women. Perinatally infected infants usually begin to excrete virus between 3 and 12 weeks of age. making early viral isolation studies essential to the diagnosis of a true congenital infection. Congenital CMV infection. and 90% of those demonstrate typical cytomegalic inclusion disease (CID). In lower SES groups. which may experience a mortality rate as high as 30%. being approximately one ninth as great as after primary infection. CMVs may be transmitted either vertically (that is. characterized by involvement of the central nervous system and reticuloendothelial system. 176-4)/.

congenital heart defects. With the vaccine-related decline in congenital rubella. Laboratory-based case identification permitted documentation of subclinical rubella infection in expectant mothers. along with congenital cataracts and heart defects. During the 1963-1965 rubella epidemic in the USA. has yet to bear fruit. Initial estimates of fetal damage following firsttrimester maternal rubella ranged from 16% to 59%. 49% were clinically apparent and 51% were subclinical. thrombocytopenia. Although prognosis for life with normal neurologic development among these infants is better. reiterating the need for longitudinal screening programs during the preschool years. Included in the expanded rubella syndrome are deafness. as well as a safe and effective treatment regimen. thus pinpointing the exact timing of maternal rubella infection. Such subclinical infections. microcephaly. SNHL is the most common irreversible sequela of congenital cytomegalovirus infection. may become apparent months to years after birth. It is bilateral in about 50% of cases. Congenital rubella During the Australian rubella epidemic of 1941. clinical or subclinical. and semicircular canals. or ganglia. approximately 10% to 15% will develop significant SNHL. speculation regarding the dire outcome of congenital CMV infection was based solely on data from the 10% of congenitally infected infants who are symptomatic. interstitial pneumonitis. saccule. endolymphatic hydrops was noted to be present in at least a portion of each cochlear duct. research directed toward developing a clinically effective vaccine. which account for 90% of congenitally infected infants.Before current viral isolation techniques were available. Although no inclusion-bearing cells were present in the organ of Corti. Prospective studies were carried out by obtaining paired sera sampes from pregnant women. as well as confirmation of congenital rubella infection in infants who did not manifest all components of the classical rubella syndrome. cristae. cataracts. mental or motor retardation. Following isolation of the rubella myxovirus in 1962. Of 165 laboratory-documented cases of maternal rubella in one study. Reissner's membrane. Stagno and coworkers (1982) found that nearly 25% of SNHL either develops or increases in severity after the first year of life. Infants with only one or two 16 . newborn hepatosplenomegaly. and mental-motor retardation. ranging from mild to profound. Investigators were unaware of the large percentage of asymptomatic infected neonates. radiolucencies in long bones. Swan and coworkers (1943) were first to describe deafness as a component of the rubella triad. Histopathologic study of temporal bones of infants dying of CID has revealed characteristic inclusion bodies in the superficial cells of the stria vascularis. the limbus spiralis. utricle. varying in magnitude from 50 to 100 dB. and low birth weight. with an estimated 30% to 50% incidence in symptomatic cases and 10% to 15% in asymptomatic infants with congenital infection. microcephaly. encephalitis. eye defects. the ophthalmologist Gregg (1941) first recognized the teratogenic potential of prenatal maternal infection. Maternal rubella during the first trimester of pregnancy exacted the greatest toll on the fetus. Whereas rubella occurs in epidemic cycles. these laboratory methods for documenting the presence and timing of rubella infection led to the description of rubella-related disorders in addition to the classical triad. but some offspring of mothers with second-trimester infection were also found to have deafness. Thus far. clinically applicable methods for confirmation of infection by serologic and virus isolation techniques became feasible. congenital CMV infection is likely the most common cause of nongenetic congenital sensorineural deafness in developed countries. CMV infection extracts an anually recurring toll on the newborn population.

Before the availability of an effective rubella vaccine. Partial collapse of Reissner's membrane with adherence to the stria vascularis and organ of Corti was observed in a number of cases. The organ of Corti per se was relatively unaffected but the stria vascularis was noted to be smaller than normal and areas of cystic dilatation were observed at the junction of Reissner's membrane and the spiral ligament. Viral excretion can pose a hazard to rubella-susceptible health care and child care personnel interacting with infected babies. Widespread and. Saccular collapse with histologic evidence of recent acute inflammation was documented in a number of temporal bones. and spiral ganglion were unaffected. As a consequence. Temporal bone histopathologic findings in rubella infants include Scheibe-type cochleosaccular changes. falling to less than 1% in non-epidemic years. Some patients showed no response at any frequency. The hearing loss was typically sensorineural in character. and it must be considered as an etiologic possibility in immigrant children with sensorineural hearing impairment. appear to become more susceptible to the effects of intracellular virus with increasing cellular specialization. 57% had hearing impairment. being the only defect found in 22% of cases. Up to 60% of cases of newly identified deafness in infants and young children were attributed to prenatal rubella in epidemic years. epidemics in most developed countires occurred at 6. mandatory administration of the rubella vaccine to children and nonpregnant women of childbearing age in the USA has markedly decreased the incidence of rubella. Serial audiograms demonstrated a progressive decrease of auditory acuity in 25% of cases. ranging in severity from patient to patient and to a lesser extent between the ears of the same patient. Prolonged virus shedding was observed in many infants who failed to thrive. In some sections the tectorial membrane was found to be rolled and lying in the internal sulcus. prenatal rubella still poses a threat to 9-year intervals. Approximately 30% of babies born of mothers with subclinical but laboratory-confirmed infection had hearing loss. 17 . whereas 41.5% of infants in whom only serologic confirmation could be obtained were hearing impaired. such as fiber cells in the lens of the eye. semicircular canals. Among those infants from whom rubella virus was isolated.components of the rubella triad were clearly demonstrated to be victims of congenital rubella infection. Hearing loss was the single most common deficit in the laboratory-documented congenital rubella population. most of whom were progeny of mothers with first-trimester rubella. but the most frequently observed audiometric curves were of the "cookie-bite" type with greatest loss in the middle frequencies between 500 and 2000 Hz. In some parts of the world. gradual progression in cataract formation was noted in the postnatal period. however. A general miniaturization of organs from rubella-infected fetuses and infants was noted at autopsy. but the utricle. Highly specialized cells. and histopathologic examination revealed hypocellularity. in some instances.

as well as excluding other disease processes that may mimic the condition. Congenital toxoplasmosis Toxoplasmosis is spread by the ingestion of oocysts on food contaminated by cat feces or consumption of tissue cysts in undercooked meat products. 18 . represents the only definitive means of diagnosing HSE. the more common neurologically dominant type and a disseminated variant with multiple organ system involvement. in addition to acyclovir. through which fetal infection occurs. Except in immunocompromised mothers. On the other hand. congenital toxoplasmosis is subclinical and must be confirmed by laboratory studies. In 90% of cases. A large percentage of HSVinfected neonates are born prematurely of young. Effective team management of a child with HSE requires the involvement of neurologists. greater fetal damage follows first-trimester infection. and ingested feline fecal material containing oocysts leads to the liberation of organisms that invade human intestinal mucosa and are widely disseminated. until definitive diagnostic tests have been completed. pulmonologists. are accompanied by abnormal CSF findings in over 90% of patients. Neonatal HSV patients may present with mucocutaneous involvement or disseminated infection. fetal infection is usually the result of primary maternal infection during gestation.Herpes simplex encephalitis Herpes simplex encephalitis (HSE) is uncommon. The route by which the HSV reaches the brain during primary infection is not clear. and infectious disease specialists. and generalized intracranial calcifications. Epidemiologically. Chemotherapy for HSE involves the antiviral drug acyclovir for a 10. Two clinical forms are recognized. The cat is the definitive natural host for the protozoan organism Toxoplasma gondii. direct spread from the nasopharynx via the cribriform plate. Cysts may be formed in all tissues of the body including the human placenta. but 25% to 30% of cases involve the pediatric age group. recent studies reveal a tenfold increase in the incidence of neonatal HSV (herpes simplex virus) infection. is most likely to occur in the second or third postpartum week. as well as by congenital transmission. Such infants have a very poor prognosis for normal development. with one fourth to one third of the infants also affected by meningoencephalitis. Herpes simplex meningoencephalitis. Although the incidence of fetal infection is greater if maternal infection occurs during the third trimester. Electroencephalography and imaging studies. which has an incubation period ranging up to 4 weeks. which is positive in 33% to 55% of HSE 14-day period. including fever and an altered mental state. Nonspecific clinical findings. Brain biopsy. hydrocephalus. neurosurgeons. Clinical presentation of congenital Toxoplasma infection may include chorioretinitis. up to 20% of newborns with HSV infection never manifest cutaneous involvement. intensivists. computerized tomographic scanning. and retrograde spread from infected ganglia have all been postulated. The infection has demonstrated a predilection for the temporal and frontal areas of the brain. often nulliparous mothers. although hematogenous dissemination. Clinicians caring for a child with undiagnosed focal encephalitis are advised to introduce broad-spectrum antimicrobial therapy. so that the absence of a positive history does not exclude the disease. If subclinical infection is unrecognized and consequently untreated. and magnetic resonance imaging are of benefit in detecting focal meningoencephalitis. As anticipated in light of the rapidity rising incidence of genital herpes infection in women of childbearing age. only 50% of neonatal HSV infections can be related by history to a definite maternal or paternal infection.

including deafness. demonstrating that adequate treatment of primary maternal infection during pregnancy reduces the likelihood of transmission to the fetus. Infected infants should receive very careful follow-up.there is a high likelihood of subsequent chorioretinitis with decreasing visual acuity. congenital infection occurred in 0. Prenatal and neonatal evaluation of the fetus and infant can document congenital infection so that postnatal treatment can be instituted as early as possible. begun at birth. and precocious puberty. Inoculation of fetal blood and amniotic fluid into mice. progressive CNS involvement with decreased intellectual function. including CT scans to assess central nervous system status and ophthalmologic examination for chorioretinitis. deafness. Prenatal diagnosis of fetal infection is accomplished by acquisition of amniotic fluid through amniocentesis and fetal blood samples from the umbilical cord under ultrasound control. Stepick-Biek. Prompt and intensive maternal treatment with a combination of pyrimethamine plus a sulfonamide of the sulfapyrimidine type is advocated as a means of decreasing the likelihood and mitigating the effects of fetal 25-week group was 70% less than reported in previous studies. with estimates ranging from 1:1000 to 1:8000. 1990). Decoster et al. The most effective strategy for control of fetal damage is prevention of maternal infection by careful attention to hygienic measures. and compulsory programs for the identification of seronegative women early in pregnancy have been implemented in that country (Daffos. The relatively low incidence of fetal infection among the 16. 1988. and in 20% of infants born after maternal infection during the sixteenth through the twenty-fifth week of pregnancy. which included prenatal treatment of maternal infection. 1974. including cleaning of fruits and vegetables and thorough cooking of meat products. Expectant mothers should be especially careful when cleaning cat litter boxes. It is estimated that as many as 85% to 90% of American women of childbearing age may be previously uninfected and consequently at risk for primary infection. IgM immunosorbent assays. Extended treatment is also advocated for congenitally infected infants. in 3.7% of fetuses carried by mothers who were infected from the sixth to the sixteenth week of gestation. French investigators found that treatment of congenitally infected infants. 19 . in the form of alternating courses of pyrimethamine and sulfonamide. Careful serologic testing of women at the time of diagnosis of pregnancy and during prenatal visits will facilitate accurate identification of seroconverters and prompt institution of maternal treatment during pregnancy. In the French studies. Maternal infection is confirmed by the appearance of specific IgG in a previously seronegative patient or a rising IgG titer after a 3-week or greater interval. reduced the frequency of chorioretinitis from 60% to 10%.6% of cases with documented maternal infection during the preconceptual/early pregnancy perion. Longitudinal follow-up studies in France should further demonstrate the effectiveness of recommended treatment regimens in preventing sequelae. French investigators conducted extensive studies of pregnancies at risk for congenital toxoplasmosis. Accurate incidence figures for congenital toxoplasmosis in the USA are elusive. Desmonts and Couvreur. 1988. and quantitative maternal and fetal IgG studies are utilized to document the presence of fetal infection.

Prevalence estimates of hearing loss among patients with congenital syphilis range from 3% to 38%. reports from large otologic centers indicate a prevalence of 570/100. both antitreponemal IgM and IgG antibodies are present. usually without vertigo. a complex and costly but highly specific (99%) procedure. The most widely utilized treponema-specific test is the fluorescent treponema antibody absorpion test (FTA-ABS) with a high sensitivity rate to all stages of syphilis and a low rate of false-positive results. Recent reports indicate a rapid increase in the number of acquired and congenital syphilis cases. There is evidence that concurrent human immunodeficiency virus (HIV) infection in patients with acquired syphilis may increase the likelihood of early progression to neurosyphilis and be associated with failure to respond to penicllin therapy.Syphilis Congenital syphilis.000 of presumed otosyphilis among otologic referrals. and later acquired syphilis. In the presence of active infection. and caloric responses weak to absent. Nonspecific tests are utilized for screening large numbers of patients from low-incidence populations. which may present in children as a sudden. bilateral profound impairment. In some instances. A positive labyrinthine fistula test may be present (Hennebert's sign). and Tullio's phenomenon (dysequilibrium in response to loud sounds) may be observed. Although SNHL has been reported in patients with primary. Treponema pallidum infection gives rise to both nonspecific reagin antibody and specific antitreponemal antibodies. Birdsall and coworkers (1990) introduced a western blot assay to identify antitreponeaml antibody isotype and determine whether or not the infection remains active. Speech discrimination scores tend to be poorer than expected from the audiometric configuration. 20 . After successful treatment. and nasal septal perforation. pallidum inhibition test. Other treponema-specific tests that may be used to confirm FTA-ABS results are the micro-hemagglutination assay for T. with about 37% of cases presenting before 10 years of age. asymmetric. A commonly reported audiometric configuration is a bilateral. may be manifest at birth or may be inapparent until as late as the fifth decade of life. only IgG antibodies persist. flat sensorineural hearing loss. or progressive. On the other hand. Because any attempt to carry out direct dark-field examination of perilymph for Treponema pallidum would present an unacceptable risk of additional hearing loss. sensorineural hearing loss may be the only presenting symptom. In late congenital syphilis the hearing loss may be sudden. the specificity rate approaches 98% in large studies. resulting from the transplacental transmission of the causative organism Treponema pallidum to the fetus after the fourth month of gestation. serologic tests present the best alternative means for diagnosing otosyphilis. the primary concern in children is congenital infection. such as systemic lupus erythematosus. fluctuating. secondary. loudness recruitment severe. interstitial keratitis. such as state-required tests of cord blood from all newborns. Hutchinson's teeth (notched incisors). Because the treponema-specific tests may remain positive following adequate treatment. justifying the use of more expensive treponema-specific procedures. accompanied in many cases by episodic tinnitus and vertigo. 51% between 25 and 35 years of age. and 12% becoming apparent even later in life. pallidum (MHA-TP) and the T. Classic stigmata of congenital syphilis include deafness. Most instances of false-positive results involve autoimmune or drug-induced collagen vascular diseases.

which may add a conductive component to a preexisting sensorineural hearing loss. initially administered in a gradually tapered dosage regimen. Gummatous changes may be found in all bones of the ear including the ossicles. suppression of immune reaction to spirochetal antigens.High-dose parenteral penicillin is the treatment of choice in all nonallergic patients with a presumptive diagnosis of otosyphilis. As an adjunct to adequate antimicrobial therapy. as well as involvement of the stria vascularis. Osteitis of the temporal bone with secondary involvement of the membranous labyrinth can also be found in late congenital otosyphilis. Relative contraindications to steroid therapy include lack of immunity to varicella. with round cell infiltration but may also present as a meningolabyrinthitis. Greater improvement is usually observed in speech discrimination scores than in pure-tone thresholds. and varying degrees of tissue necrosis. osteitis of the otic capsule. bone growth disturbance. pregnancy. and eighth nerve fibers. The bacterial pathovens involved may vary from center to center. spiral ganglion. carries a significant mortality. such as cataract formation. Meningitis is a common outcome of bacteremia in these infants. The discovery that treponemes may lie dormant for as long as 90 days between replications in late congenital syphilis cases dictates the necessity for longerterm treatment schedules than formerly recommended. has been reported. as well as mononuclear cell infiltrates. which should be consulted before initiating therapy. Atrophy of the organ of Corti. Steroids. recent vaccination. and adrenal suppression. Fatal cases of varicella have been reported in young children receiving steroid therapy. with an inverse relationship to the age and weight of the child. as well as the eighth nerve. and consideration must be given. to the potential limits on penicillin diffusion posed by the blood-CSF and blood-perilymph barriers. and appropriate evaluation with techniques such as auditory brain stem response testing should be undertaken. and careful case selection is essential. diabetes mellitus. hypertension. long-term maintenance therapy may be required to sustain hearing improvement. Temporal bone histopathologic features in cases of congenital otosyphilis include obliterative endarteritis. Postmeningitic deafness should be suspected in all survivors of neonatal meningitis. characterized by signs of infection and septicemia in the first month of life. in dosage determination. ranging from 10% to 50%. Neonatal sepsis Neonatal sepsis. are usually discontinued after 4 to 8 weeks if hearing does not improve. but group B streptococci and gram-negative enteric bacilli are most commonly observed. Current recommendations for dosage and treatment course may be found in publications from the Centers for Disease Control. On the other hand. Alternate-day dosage appears to carry less risk of sequelae. systemically administered corticosteroids (generally oral prednisone) have demonstrated effectiveness in stabilizing or improving hearing in approximately 50% of patients with syphilitic deafness. 21 . and uncommon organisms such as Listeria monocytogenes may play a significant role in such cases. glaucoma. Early congenital syphilis may involve the labyrinth. and peptic ulcer disease. The mechanisms of steroid action in these cases are uncertain but may involve nonspecific reduction of vasculitis. or enhancement of penicillin diffusion into the perilymph.

The perilymphatic system. Collapse of Reissner's membrane with adherence to underlying structures has also been described. predisposes to the onset of inflammation in this structure. Intralabyrinthine fibrosis and osteoneogenesis in perilymphatic spaces were found in patients who had survived the acute disease process. Among this group of infants. Sluggish strial circulation. These histopathologic changes are also compatible with findings in cases of SNHL caused by prenatal rubella. 22 . Bacterial meningitis Bacterial meningitis in young children was associated with a 90% to 100% mortality during the preantibiotic era. the tectorial membrane. contrasted with lesser degrees of involvement of neural structures in the cochlear duct. The highest percentage of childhood meningitis cases in the USA occur in children 6 to 9 months of age. Two distinct pathogenetic mechanisms have been implicated in SNHL as a sequela of measles or mumps. and Streptococcus pneumoniae collectively accounting for 84% of cases. coupled with an intraepithelial capillary network. Neisseria meningitidis. clinical investigators reported a mortality of 2% to 3% among children over the age of 1 month with bacterial meningitis that had been adequately treated. Escherichia coli and group B beta-hemolytic streptococci are the most common causative organisms. Temporal bones from infants who died during the acute stage of meningoencephalitis demonstrate lymphocytic infiltration along nerves and vessels in the internal auditory canal without concurrent involvement of the stria vascularis. with Haemophilus influenzae.Later-onset infectious disease Mumps and measles Measles and mumps immunization as part of standard well-baby care has effected a 90% to 95% decrease in the incidence of these diseases in the USA. By 1986. and the internal auditory canal contents are generally uninvolved. Temporal bone findings in patients who suffered meningoencephalitis in conjunction with measles or mumps are substantially similar to those associated with meningogenic bacterial labyrinthitis. the most common otologic sequela attributed to this virus was unilateral profound SNHL or unilateral anacusis without vertigo or vestibular impairment. proceeding from the cochlear base to the apex. the organ of Corti. the vestibular sensory organs. In cases of SNHL without signs of meningoencephalitis. the virus appears to access the inner ear via the stria vascularis during viremia. which is followed by degeneration and scarring. It appears that direct extension of the viral inflammatory process occurs along the nerves and vessels in the internal auditory meatus into the inner ear. H. Data from adults suggest that the time of onset of mumps hearing loss is usually within a few days after the disease has reached the acute stage. influenzae is the most commonly isolated pathogen. In cases of neonatal meningitis. and peripheral cochlear neurons. Before the availability of an effective vaccine for mumps. The resultant change in the volume and constitution of endolymph has been invoked to explain subsequent degeneration of the stria vascularis. Findings compatible with such a transmeatal route of infection include severe degeneration of neural elements inthe modiolus.

and learning disabilities. asymmetric SNHL and 11% to have unilateral SNHL. in some cases. or fluctuation of auditory acuity often require a year or more to stabilize following meningitis. (2) serous or toxic labyrinthitis that constitutes a sterile inflammatory response. or neuritis of the eighth nerve. vestibular deficits. Thresholds in patients who exhibit improvement. The onset of hearing loss associated with bacterial meningitis usually occurs early in the course of the disease. poor impulse control. and at least one handicap was detected during a 1-year follow-up in 57% of pneumococcal meningitis survivors and 14.Unfortunately. rather than severe or profound. the dramatic decline in mortality was not accompanied by a concomitant decrease in the incidence of immediate and long-term sequelae of the disease. Direct spread of the infection to the labyrinth from the middle ear during a bout of otitis media is much less likely than (1) the penetration of bacteria and toxins along the cochlear aqueduct or internal auditory canal leading to a suppurative labyrinthitis. In my series of 280 meningitis survivors. The likely pathophysiologic explanation for changing bone conduction thresholds during and after an episode of bacterial meningitis is the occurence of serous labyrinthitis. and no particular regimen of antibiotic therapy appears to offer any degree of protection against this sequela. Apart from sensorineural hearing impairment. These reports can be broadly classified into those using behavioral audiologic tests and those using primarily ABR (Tables 176-1 and 176-2). and brain/spinal cord necrosis. seizure disorders. arterial occlusion. language disorders. A number of observations can be drawn from these studies. Some reports have documented improvement in hearing acuity in a small number of cases observed longitudinally. Some patients with improving thresholds continue to exhibit absent vestibular responses. quadriplegia.5% of children in which H. 1988). diplegia. is also distinctly uncommon. meningitis sequelae may include mental retardation. whereas in other patients hearing losses fluctuated or progressed. motor abnormalities (hemiparesis. Most patients with postmeningitic losses who show improvement of auditory thresholds over time initially demonstrate mild or moderate. Meningitis patients who exhibit normal ABR after the first few days of hospitalization and antibiotic therapy are unlikely to develop later SNHL. The reported incidence of SNHL following meningitis varies from3% to 40%. visual impairment. speech defects. bilateral. (3) septic thrombophlebitis or embolization of small labyrinthine vessels. influenzae was the etiologic agent. hyperactivity. These findings are consistent with recent observations regarding the role that the hosts's initial inflammatory response may have in damage sustained by neural tissue. SNHL. Late-onset SNHL. Computerized tomographic imaging studies of the CNS in children with severe sequelae reveal evidence of brain infarction. 89% of those who experienced postmeningitic hearing loss contracted the disease before their third birthday (Brookhauser et al. after discharge from the hospital. perineuritis. and (4) hypoxic insult to the eighth nerve or central auditory pathways. but in a series of 64 carefully documented cases. These observations may. The majority of patients with post-meningitic hearing loss sustain permanent. Some patients whose ABR results are abnormal early in their hospital course may demonstrate a normal ABR by the time of discharge or in follow-up evaluation. Seizures are experienced by 28% to 40% of meningitis patients before or during their hospital stay. with most reports clustered in the 15% to 20% range. hydrocephalus. coworkers and I found 38% to have bilateral. deterioration. severe-to-profound sensorineural impairment. cerebral palsy). All meningitis survivors should have careful evaluation of 23 . reflect the resolution of a co-existing conductive loss caused by middle ear effusion.

other strategies for downmodulating host response to the infection are being explored in current studies. 24 . The damage attributable to such an inflammatory reaction was first demonstrated in animal studies of pneumococcal meningitis and later with gram-negative pathogens. Because postmeningitis hearing losses may assume a wide range of audiometric configurations. such as decreased glucose levels. may be attributable to direct bacterial action on nervous tissue. Careful longitudinal follow-up of postmeningitis children will avoid diagnostic errors. Laebel et al. In double-blind. The local production of interleukin-1B (IL-1B) and tumor necrosis factor (TNF) in response to CNS tissue interacting with bacterial breakdown products is thought to be the first step in a complex series of molecular events that result in inflammation and tissue destruction. were significantly less pronounced after 24 hours of combined therapy with antibiotics and dexamethasone than with antibiotics alone (Odio et al.auditory function. stimulating an intense immunologic response by the host. to be followed by behavioral audiologic testing when the child's condition permits. Because of a natural reluctance by some clinicians to administer steroids in the face of a potentially life-threatening infection. Based on the hypothesis that down-modulation of the host inflammatory response could ameliorate the severity of postmeningitic sequelae. the patient's inflammatory response. click-evoked ABR. elevated protein. Neurologic sequelae of bacterial meningitis. 1988). In a population of 200 infants and older children. placebo-controlled trials with bacterial meningitis patients. Bacterial disintegration resulting from antibiotic action produces a veritable flood of cell wall antigens and endotoxins. initially by ABR in younger children. CNS indices of infection severity. which assesses hearing sensitivity primarily in the high-frequency region (2000 to 4000 Hz) may lead to erroneous conclusions regarding auditory acuity at lower frequencies. 1988). Experimental animal models demonstrate that bacterial surface components. thromboxane. It is hypothesized that inflammatory exudate that forms as a result of meningeal invasion by bacteria is potentially harmful and is not critical for containment of the infection. are sufficient to produce the symptom complex of meningitis even in the absence of viable bacteria. Corticosteroids act to inhibit the activity of phospholipase with a consequent decrease in prostaglandin E2. including endotoxin and cell wall structures. By studying paired CSF samples drawn at admission and 18 to 30 hours later. patients receiving dexamethasone became afebrile earlier and were less likely to suffer moderate to severe sensorineural hearing loss than controls. 1991. and leukotriene formation. Fourteen percent of patients in the placebo group had severe or profound hearing loss. whereas only 1% of the steroid-treated group were affected (Laebel et al. Studies of the progression of events at the molecular level during an episode of bacterial meningitis suggest that significant injury to the central nervous system occurs during the first hours of antibiotic therapy. Poorer outcome observed in neonates receiving intraventricular gentamicin rather than just intravenous antibiotics may also be attributable to the patient's response to an additional load of bacterial degradation products in the CSF. including sensorineural hearing loss. or a combination of both factors. clinical investigators have found a correlation between the intensity of inflammation as reflected in CSF findings and subsequent clinical outcome. Dexamethasone has also been shown to decrease the production of IL-1B and TNF. corticosteroids have been used as adjunctive therapy to the usual course of bactericidal antibiotics. Reports involving neonates and young children with meningitis have also documented a rapid host inflammatory response following antibiotic-induced release of bacterial components. and increased lactate levels.

Salicylates e. 25 . Carbon monoxide b. Mercury c. Chemicals a. Neomycin d. Polybrene f. Aniline dyes 3. Vancomycin g. Cisplatin b. Nitrogen mustard g. Chloroquine d. A partial listing of drugs and chemicals with ototoxic potential follows: 1. Kanamycin f. a steadily increasing number of potentially ototoxic drugs and chemicals are being identified. Gentamicin e. Dihydrostreptomycin c. Other ototoxic drugs and chemicals produce more profound effects after the sensory end-organ of the inner ear has reached a greater degree of differentiation later in pregnancy. or inner ear with associated sensorineural hearing loss. Thalidomide. Gold d. middle. Streptomycin b. Polymyxin B h. Furosemide 4.Ototoxic Drugs and Chemicals As a result of more accurate reporting of adverse effects of pharmaceutical agents mandated by federal regulations. Erythromycin 2. Arsenic f. taken early in pregnancy produce severe embryopathic effects that may include deformities of the external. Some medications. Antibiotics a. Loop diuretics a. Lead e. such as thalidomide. Quinine c. Other drugs a. Ethacrynic acid b.

000 Hz. other factors thought to predispose to aminoglycoside ototoxicity include preexisting hearing loss. 25 to 45 days) increases the risk of damage as does concomitant administration of other ototoxic drugs. In addition to compromised renal function. Streptomycin. age. The margin between therapeutically effective blood levels and potentially toxic concentrations for aminoglycosides is relatively small. prior use of aminoglycosides. and tobramycin are primarily vestibulotoxic. temporally related noise exposure. type I hair cells of the crista ampullaris appear to be more sensitive to damage by streptomycin. Dosage levels must be adjusted downward appropriated in patients with renal dysfunction. duration of therapy. and vestibular evaluation may be of benefit for providing early warning of impending damage. whereas kanamycin and amikacin are principally chochleotoxic. perrotatory stimulation with a torsion swing. and Reissner's membrane. Hemodialysis and peritoneal dialysis are effective in lowering serum levels in renal-compromised patients. conducted controlled prospective studies of infants receiving aminoglycosides for neonatal sepsis. Cochlear damage usually proceeds from the basilar turn toward the apex with initial destruction being observed in the inner row of outer hair cells. This class of antimicrobials is not metabolized in the body and is excreted almost entirely by glomerular filtration so that urinary concentrations can approach 100 times serum levels if renal function is impaired. Prolonged administration of the drugs (that is. Although the remaining rows of outer hair cells may also be destroyed. including frequencies above 12. kanamycin. Fee (1980) observed that gentamicin was significantly more vestibulotoxic than tobramycin. 26 . Finitzo-Hieber and colleagues (1985) concluded that aminoglycosides at appropriate dosage levels pose little risk of ototoxicity in children. elevated creatinine clearance. Normal serum half-life is about 2 hours in patients with unimpaired renal function. Schacht (1986) demonstrated that the drugs are transmitted into hair cells by an energy-dependent process involving binding to the phospholipid phosphatidyl-inositol biophosphate.Aminoglycosides Aminoglycoside antibiotics are administered parenterally because they are poorly absorbed from the gastrointestinal tract. It has been documented that aminoglycosides may also accumulate in the perilymph. particularly in patients with suboptimal renal function. gentamicin. Serial audiometric screening. Aminoglycosides are utilized with some regularity to treat serious infections in neonates and young infants. Histopathologic evidence of injury has been observed in the stria vascularis. ethacrynic acid and furosemide). and caloric irrigations. Eviatar and Eviatar (1982). inner hair cells are usually spared except in cases of overwhelming toxicity. pericapillary tissues in the spiral prominence. and gentamicin than type II. the toxicity being further potentiated by high hematocrit. but controversy exists as to the inherent risk posed to hearing and balance function. with only 3% actually entering the bloodstream. suprastrial spiral ligament. evaluating such parameters as acquisition of head control and nystagmus induced by position change. Nearly 10% of the infants who had received aminoglycosides demonstrated vestibular abnormalities and delay in acquisition of head control as would be compatible with vestibulotoxicity. criticality of illness. so that careful monitoring of peak serum levels (30 minutes after intravenous administration) and tough levels (immediately before the next IV dose) is essential. the outer sulcus. On the basis of extensive studies. however. and duration of therapy beyond 10 days. In the vestibular system. or concomitant use of additional ototoxic drugs such as other aminoglycosides and loop diuretics (for example.

was noted in adults with erythromycin doses of 2 g/day. Bilateral SNHL. Vancomycin Nephrotoxicity and ototoxicity have been reported in patients receiving vancomycin. particularly if blood levels exceed 45 mg/L. cochlear adenosine triphosphate levels. Matz (1990) reports that premature infants are more susceptible to the ototoxic effects than full-term babies because they have larger volumes of distribution of the drug. Early clinical observations of a transient ototoxic effect associated with the use of these agents were followed by reports of permanent ototoxicity. Blood levels at which ototoxic effects were observed ranged upward from 63 mg/L. which has a longer half-life in these neonates. promote the rapid excretion of large amounts of isoosmotic urine. Adults have described tinnitus at slightly lower serum levels. Estimates of the incidence of ototoxic effects with this class of pharmaceuticals reported by Matz (1990) range from 0. Hawkins' work (1973) demonstrated that salicylates in the perilymph can lead to a reduction in transaminases. such as ethacrynic acid and furosemide. particularly in patients with concomitant renal or hepatic failure. The association of the ingestion of therapeutic doses of salicylate in young febrile children with the occurrence of Reye's syndrome has led to a marked decrease in the utilization of this class of drugs in the pediatric and adolescent age groups without strict indications.Some investigators report partial return of vestibular function after an initial deficit has been demonstrated during extended gentamicin therapy. Temporal bone histopathology in animals treated with toxic levels of these drugs reveals changes in the stria vascularis and significant hair cell loss. particularly when these diuretics are used concurrently with apparently safe levels of aminoglycosides. Changes in cochlear function have been attributed to a salicylate-mediated increase in the membrane conductance of outer hair cells. which could serve as early warning of impending damage.4% with furosemide. Rybak and coworkers (1990) postulate that furosemide and ethacrynic acid have different mechanisms of action on the cochlea.7% with ethacrynic acid to 6. 27 . Loop diuretics Powerful "loop" diuretics. the respective dosages of these medications should be carefully adjusted when they are administered concurrently. Salicylates High therapeutic doses of salicylates (levels exceeding 20 mg/dL) are known to be associated with reversible hearing loss and tinnitus in humans. often accompanied by tinnitus and vertigo. Erythromycin The ototoxic potential of erythromycin became evident with the relatively large intravenous dosage levels utilized to treat pneumonia caused by Legionella pneumophilla. Because of the repeatedly documented synergy between the ototoxic effects of loop diuretics and aminoglycosides. and cochlear blood flow.

15 dB at two frequencies. The pathophysiologic mechanism by which damage occurs involves drug-mediated blockade of outer hair cell transduction channels. has been implicated as an ototoxic agent. primary apnea. outer hair cell loss is observed.000 Hz and 14. principally at higher frequencies. Histopathologically. Both retinopathy and hearing loss have been observed in offspring of pregnant mothers treated with chloroquine. Studies employing serial high-frequency audiometry demonstrate that the hearing loss usually begins in the 10. or 10 dB at four frequencies. resulting from such factors as cord compression and neonatal seizures.000 Hz has proven helpful in early identification of ototoxicity. particularly in the basal turn of the cochlea. In a study evaluating thresholds from 8 to 20 kHz. postnatal apneic episodes. producing greater hair cell loss and hearing impairment at high frequencies in combination than is observed with either agent alone. Anoxia/Hypoxia Anoxia and hypoxia during the perinatal period. bilateral. including deterioration of 20 dB or more at one frequency. with the potential for permanently affecting both cochlear and vestibular function. low Apgar scores at 1 and 5 minutes. Early estimates placed the risk at 20% or less. The pathophysiologic mechanism involved with both drugs appears to be vasculitis and ischemia in the inner ear. a history of resuscitation at birth.000 to 18. Dreschler and colleagues (1985) utilized conservative criteria for damage. Audiometric screening at 12. high-frequency sensorineural hearing loss was detected in 88% of children receiving cisplatin doses over 450 mg/m2.Cisplatin Cisplatin (cis-diaminoedichloroplatinum). with subsequent degenerative changes of the stria vascularis. are strongly correlated. In one report of 54 cases. Estimates of the risk of ototoxicity posed by cisplatin vary with the audiometric frequencies that are evaluated. They found that 46% to 83% of patients in the various study groups demonstrated some degree of loss. Mothers receiving quinine during pregnancy may give birth to infants with varying degrees of severe to profound hearing impairment. gradually involving frequencies below 8.000 Hz range. was inversely proportional to the age of the child. organ of Corti. with the remainder having unilateral involvement. Although conclusive human studies addressing this issue are not available. Animal studies have confirmed that the ototoxic effects of noise exposure (85 dB SPL or greater) and cisplatin are synergistic. Davidson and coworkers (1989) reported that permanent. coupled with a decrease in adenylate cyclase. Most investigators agree that dosage levels exceeding 3 to 4 mg/kg of body weight carry a definite risk of ototoxicity. prudence would dictate avoidance of exposure to potentially damaging sound levels during cisplatin treatment. Eighty percent of these losses were bilateral. statistically.000 Hz if treatment continues. Quinine and chloroquine The antimalarial agents quinine and chloroquine phosphate have both demonstrated ototoxic potential. Cochlear damage. which is utilized for treating a range of neoplasms. no ototoxic changes were noted in patients where the peak plasma concentration of cisplatin did not exceed 1 microg/L. which was related to cumulative doses exceeding 279 mg/m2. with subsequent SNHL in young adults. and the need for prolonged postnatal 28 . and neuronal elements. Objective evidence of anoxia/hypoxia in the neonatal history can include meconium staining.

As many as 2% of all infants with birth weight of 3 pounds or less manifest significant SNHL. with associated kernicterus. Audiologic evaluation and habilitation of these hearing impaired infants may be further complicated by the presence of additional handicaps. and kernicterus. sepsis. the middle and inner ears of these patients are generally free of abnormality. such as perinatal hypoxia. Studies of round window permeability in experimental animals suggest a greater risk for penetration by middle ear contents into the inner ear than has been observed empirically in humans. and SNHL has been appreciated for decades. resulting in neurologic sequelae including SNHL. particularly the ventrocochlear nucleus. topical medications with ototoxic potential. Mechanisms postulated to account for this observation include penetration of the labyrinthine windows (particularly the round window membrane) by infectious by-products or toxins. Histopathologic evidence demonstrates that anoxic damage occurs in the brain stem reticular formation and cochlear nuclei. In some cases of perinatal anoxia. making the precise role of oxygen deprivation in the etiology of hearing loss unclear. recent studies among neonates with chronic hypoxemia resulting from persistent fetal circulation revealed a 20% incidence of SNHL. prematurity itself constitutes a reliable risk indicator. It has been postulated that edema and granulation tissue that accompany middle ear infection may actually help prevent transmission of unwanted substances through the round window membrane. and phototherapy has markedly decreased the importance of hyperbilirubinemia as a cause of early acquired SNHL. 29 . Whether resulting from inadequate conjugation. may be present in premature and dysmature neonates. three fourths of which was moderate to severe and one fourth of which was profound. impaired albumin binding. Prematurity and Full-Term Low Birth Weight Although a number of high risk factors. or a combination thereof. Recurrent Otitis Media and Mastoid Disease Conductive hearing loss is the usual sequela of recurrent otitis media and mastoiditis. Improved prenatal care including the introduction of Rh immunoglobulin.ventilatory assistance. but studies by Paparella et al (1970. or increased unconjugated bilirubin production. and NICU outcome studies reveal that premature infants may be as much as 20 times more likely to be severely hearing impaired than infants of normal weight and gestational age. infants may have multiple high risk factors. Histopathologically. exchange transfusion. On the other hand. Admission to a neonatal intensive care unit (NICU) is standard care for these small infants. 1984) and others indicate that otitis-prone children showed an increased likelihood to have a coexisting sensorineural loss than would be predicted by incidence figures for the general population. Recent studies suggest that therapeutic intervention should be instituted at lower serum bilirubin levels in premature neonates than was previously thought necessary. the bilirubin that crosses the blood-brain barrier may be deposited in the basal ganglia. Hyperbilirubinemia A causal relatinship between elevated bilirubin levels in neonates. which show decreased cell numbers and volume in direct proportion to the length and severity of oxygen deprivation.

are exposed on a regular basis to hazardous sound levels that could result in hearing loss. leading to permanent sensorineural deafness or facial nerve paralysis. and 13% of these patients sustained SNHL. An infant's foreshortened ear canal can predispose to transcanal injury. which may include temporal bone fracture. but intralabyrinthine injury may produce a concurrent. whereas head trauma is a more common etiology in older children and adolescents. usually high-frequency. hearing loss. tinnitus. and is not presently amenable to medical or surgical treatment. cotton swab) inserted in the external canal. An important consequence of a typical noiseinduced hearing loss (NIHL) is difficulty in understanding speech sounds. often accompanied by tinnitus. Mild to moderate conductive hearing loss is the most common audiometric finding. Temporal bone fractures have been reported to occur in 7% of children who were admitted to the hospital following head injury. NIHL is entirely preventable except in rare cases of accidental exposure. on the farm. bloody otorrhea. and possibly vertigo. More than 20 million Americans. usually sparing inner ear and internal canal structures.8% of losses were attributed to head trauma. 10. Motor vehicle accidents. and falls are among the common etiologies for temporal bone fractures in children and adolescents. which could impair classroom performance.000 Americans have hearing losses that are at least partly attributable to damage from loud sounds. Such fractures are broadly classified as longitudinal or transverse with respect to the long axis of the temporal bone.Ear and Head Trauma Middle ear and inner ear truma can result from diverse etiologies. particularly if accompanied by ossicular injury.000. can occur at any age. a foreign body (for example. including children and adolescents. Utilizing current knowledge about ear protection. In a group of 324 children and adolescents with unilateral SNHL. About 10. as well as vertigo. More severe conductive impairment suggests possible ossicular damage. but the proliferation of potentially harmful noise sources at home. Large traumatic tympanic membrane perforations. Youngsters may be able to report symptoms such as acute pain. bicycle or skateboard mishaps. sensorineural component. Irreversible inner ear damage from loud sounds is cumulative over time. including perilymphatic fistula. and in recreational environments has placed increasing numbers of unsuspecting children and adolescents at risk (Table 176-3). impact against water while diving or water skiing. which in 35% of cases had been sustained at or before 6 years of age. 30 . and labyrinthine membrane disruption. with the longitudinal variety accounting for 70% to 90% of these injuries. Longitudinal fractures are associated with middle ear and ossicular damage. may require surgical intervention. but most heal with surprisingly little residual scarring. including a slap in the ear. Much of this noise exposure occurs in the workplace. Noise-Induced Hearing Loss Sounds of sufficient loudness and duration will produce ear damage resulting in temporary or permanent hearing loss. should be suspected in patients with fluctuating or progressive sensorineural losses. Transverse fractures often disrupt labyrinthine integrity or transect neural structures in the internal auditory canal. and skull trauma.

vacuum cleaner. loudness). assembly line 70 Restaurant. ranging from the tympanic membrane and ossicles to the organ of Corti. initially involving frequencies in the 3. and mitochondria has been observed with electron microscopy. intensity (that is. nucleus. chain saw E 100 Snowmobile. for example. as well as the susceptibility of the ear involved. as reflected in a characteristic "notch" audiometric configuration. which is termed acoustic trauma. continuous or intermittent) of the exposure. a change of a few decibels can represent a significant change in loudness. as have 31 . Damage risk criteria are based on the average responses of large numbers of subjects. as exemplified by gunfire or a firecracker. Ear damage resulting from exposure to hazardous noise levels may be classified as either acoustic trauma or noise-induced hearing loss (NIHL).000 to 6. soft whisper. With additional exosure. and rock concerts G 110 Shouting in ear. Exposure to intense sounds (greater than 140 dB(A) of short duration. and permanent hearing loss. with outer hair cells being initially affected. NIHL gradually becomes permanent. such high-intensity sound waves can disrupt virtually any structure in the ear. refrigerator 40 Principal's office 30 Quiet library. content. disco. a 20 dB sound is 10 times as loud as a 10 dB sound. motorcycle. hair dryer. severe. gunshot blast. orchestra 85 dB---------------------------------------------------------------80 Alarm clock. lysosomes. as produced by amplified music.000 Hz range. woodworking shop R 90 Traffic. Disruption of intracellular organelles. can produce immediate. and scheduling (that is. lawn mower. subway. air conditioner 50 Average home. headphones. Individual susceptibility to the damaging effects of loud sounds is variable. Current US Department of Labor regulations set the boundary between acceptable and damaging noise in the workplace at 85 dB(A) for continuous exposure during a full workday. Because the decibel scale is exponential.Table 176-3. sewing machine 60 Conversation. These devices can measure both continuous loud noise. Moderate exposure to less intense but potentially damaging sounds may cause a temporary threshold shift (TTS). so that it is difficult to predict the precise magnitude of hearing loss that will result from exposure of a specific individual to a potentially damaging sound. jet engine A 130 Jackhammer N 120 Boom cars. and intermittent. including endoplasmic reticulum. The "A" refers to a type of sound filter used in a sound level meter when measuring potentially damaging sound in the laboratory or workplace. By means of direct mechanical destruction. Loud noises signal danger dB Noise D 140 Firecrackers. band practice. Experimental evidence indicates that hair cells are the inner ear components most vulnerable to damage. The pattern of damage resulting from a specific exposure to a particular sound source depends on the frequency. duration. short-duration noises with very loud peak components. such as gunfire or an explosion.

Recent studies in birds. however. 132 to 170 dB(A) during the initial acoustic pulse of a typical gun discharge. "boom" cars. 32 . well above the discomfort level for most people. Whereas an explosion poses an obvious hearing risk to an unprotected ear. Degeneration of damaged hair cells may lead to eventual loss of auditory nerve fibers and changes in auditory areas of the central nervous system. The anatomic and physiologic changes that occur in the inner ear during a TTS are quite subtle and may be limited to swelling of hair cells and underlying afferent nerve fiber terminals that resolve during a rest period away from loud sounds. as generated by gunfire or an exploding firecracker. and loss of stereocilia. Average sound levels in a typical discotheque approximate 95 dB(A). hair cell loss will continue to increase. having the potential to produce immediate and permanent injury to sensitive inner ear structures. but practically everyone exposed to such sound levels will experience a temporary loss (TTS) often accompanied by tinnitus. fusion. whereas vascular spasm and metabolic exhaustion could also play a role in TTS. muffled hearing. The stereocilia rootlet structure. other potentially damaging environmental sounds may be less readily apparent. Adolescents employed in noisy environments. or tinnitus following use of a personal cassette player should be cautioned to modify listening habits to avoid NIHL. motorcycles. are characterized by short duration and very high sound intensity levels. With repeated exposure. exposure time can be quite long. A child who experiences a full feeling in the ear. but at rock concerts it is common to experience amplified sound as loud as 105 to 115 dB(A). Because they are portable and often used by listeners to drown out loud background noises. stagehands. Large-caliber rifles and shotguns are particularly hazardous. Sound levels attained in many "boom" cars containing very powerful stereo amplifiers and speakers may exceed 120 dB(A). Impulse noises. and there is no evidence that degenerated hair cells are ever replaced in mammals. "Walkman"). Not only the audience but also the rock musicians. and concessionaires are at risk for acquiring NIHL after prolonged exposure to these very high sound levels. may add to whatever hearing loss they sustain as a result of occupational exposure. while firecrackers produced peak levels measured at 3 m of 125 to 156 dB. Acute changes in stereocilia rootlets might alter cochlear micromechanics. Sound levels produced by toy weapons measured at a distance of 50 cm showed mean peak values from143 to 153 dB(A). including children. All individuals. Parents and public policy makers have expressed concern about hearing risks posed by exposure to rock music. appears to be affected first. and personal cassette players (for example. ushers. which anchors it into the top of the hair cell. Surveys reveal that about 80% of children in the middle elementary school age group own or use personal cassette players and 5% to 10% listen for extended periods at potentially dangerous volume settings. A child may unwittingly compensate for a temporary threshold shift by simply turning up the volume to even more hazardous levels. exposed to such high ambient sound levels for prolonged periods risk permanent NIHL.disorganization. who also engage in shooting or setting off firecrackers. Short periods of exposure during a typical concert can be experienced by most children and youth without suffering a permanent hearing loss. have documented some hair cell regeneration after initial loss following noise exposure. Personal cassette players are capable of producing sound levels in excess of 110 to 115 dB(A) at the ear.

noise exposure histories on 43 of 94 children (46%) included exposure to impulse sounds produced by fireworks or firearms. or accompanying a parent on a hunting trip or a visit to a target range. Eight of forty-seven children (17%) for 33 . 1992) reported results of a study of 114 children and adolescents (19 years old and younger) who were diagnosed as having NIHL on the basis of history and audiometric configuration. Such an omission may reflect a lack of care giver awareness of the noise levels produced by such devices. Among 70 children for whom very reliable information was available. The gender distribution of the sample was consistent with the findings of other investigators. but 26% of these losses were diagnosed in children aged 10 years or younger. all other categories included youngsters in the preschool and early elementary age groups. standard deviation of 4. The noise exposure histories were replete with descriptions of children riding with a parent on a recreational vehicle (for example.21 years). motorcycle.In a recent paper my coworkers and I (Brookhauser et al. Live or amplified music was identified in 11 of 94 (12%) cases as the principal source of noise exposure.7 years (range of 1.2 to 19. and bilateral losses were present in 72. in that 90. none of the histories mentioned either. In 42 children the loss was unilateral. The mean age of referral for evaluation was 12. Parents or guardians were asked to identify the potentially damaging noise sources to which their children was exposed. Histories of 14 of 19 children (74%) with exposure to multiple noise sources also mentioned fireworks or firearms.8 years. The age of identification of the hearing loss in relation to the type of noise source implicated in the history was also examined (Table 176-4). Although the "loud music" category contained only youth age 10 years or greater. fireworks or firearms were identified as the sole noise source in 21 of 58 (36%) children with bilateral losses and 8 of 12 (67%) youngsters with unilateral losses. Although cap pistols and noisy toys have been identified in the literature as possible hazardous noise sources. Consequently. snowmobile).3% of the affected children were males. assisting a parent in a home workshop.